Diseases and conditions that cause the destruction of cartilage within the joints pose a significant public health concern, particularly in view of the demographics of an aging population. Multiple mechanisms are involved in the degradation of articular cartilage in arthritides such as rheumatoid arthritis (RA) and osteoarthritis (OA). RA is the most common form of inflammatory arthritis, affecting 3% of women and 1% of men. OA, a non-inflammatory arthritis, is the most common form of joint disease, and is second only to cardiovascular disease as a cause of early retirement and disability.
Most treatments for joint ailments are generally systemic. Targeting a medication locally to a joint would have several advantages: increased efficacy, reduced side effects, an improved dosing schedule, and reduced cost of goods.
Current local treatments including glucocorticoids, injectable hyaluronic acid solutions, NSAIDs or other small molecules have relatively short half lives as well as systemic distribution once injected into the joint (Gerwin, et al., Adv Drug Deliv Rev, 58:226-42, 2006; Lindenhayn et al., Eur J Clin Chem Biochem, 35:355-63, 1997). Joint retention of a therapeutic can be achieved by coupling the therapeutic to a joint targeting agent (Rothenfluh et al., Nature Materials 7:248-54, 2008; WO05/097073; U.S. Pat. No. 7,067,144). However, treatments may require intra-articular injection with delivery vehicles such as liposomes, adding a layer of complexity and possible abrasion of the articulating surface.
Thus, there is a need to develop additional vehicles for efficient delivery and subsequent retention of a therapeutic in the joint.